Implantable medical devices have become critical in the management of a variety of human diseases and other conditions. The term “implantable medical device” refers to a medical device that is intended for long-term implantation within the body of a patient, i.e., implantation for periods substantially exceeding one month. One significant class of implantable medical devices is prosthetic heart valves, which are used to replace diseased and/or damaged natural heart valves. Implantable medical devices also include annuloplasty rings, internal pacemakers, and artificial hip and knee prostheses, among others. The term “insertable medical device” refers to a medical device, that may be placed within the body of a patient for short-term periods, typically a few days but less than one month. Insertable medical devices include venous and urinary catheters, among others.
Although their development has saved countless thousands of lives and improved the quality of life for millions of patients, implantable medical devices do have certain risks of complications, including inflammatory tissue responses to the implant. Serious inflammatory tissue responses following implantation occur relatively infrequently in humans, but when present they can produce costly complications resulting in the need to remove and replace the implanted device or otherwise surgically intervene to correct the complication.
Prominent among post-operative complications is the excessive growth of tissue on implantable medical devices. In the case of prosthetic heart valves, there is a need for a moderate amount of tissue ingrowth into the sewing cuff of the valve to ensure that the valve remains anchored to the heart. The end-stage healing response to biomaterials such as the heart valve sewing cuff is fibrous encapsulation of the biomaterial. When integrated with the fabric, the connective tissue that constitutes the fibrous capsule is called pannus.
Incomplete pannus leaves fabric exposed, which can lead to chronic inflammation. Excessive pannus growth, on the other hand, occupies the orifice area distrupting blood flow, which can lead to thrombosis. In addition to an increased risk of thrombosis, overgrowth of pannus onto the prosthetic valve leaflets after implantation can lead to malfunction of the valve. More specifically, pannus overgrowth can protrude into the valve annulus and reduce the annular flow area, thus interfering with valve leaflet sealing. Limited control of pannus growth on implanted medical devices has been achieved through use of Biolite® carbon coating on device surfaces, but better control of pannus growth is desirable.